Osteoporotic fractures and low bone mineral density (BMD) are serious public health burdens. Substantial evidence exists that BMD is partially determined by genetics, although to date, few genes influencing variation in BMD have been identified. The majority of genetic studies have been conducted in Caucasian populations;examining the relationship between genetics and BMD in an ethnically diverse population (Mexican Americans) and a founder population (Amish) may facilitate identification of novel genetic loci associated with BMD. Our strategy is to: 1) conduct a genome wide association study (GWAS) in two populations of large, multigenerational families;2) carry out formal meta-analysis of BMD between the two populations;and 3) conduct pathway based analyses and tests of gene-by-gene interaction among genes within these biological pathways. These research objectives were developed to complement the training component of this proposal, the objectives of which are to: 1) obtain more advance training in the genetics of BMD;2) develop expertise with contemporary methods of genetic analysis employed in GWAS;and 3) gain experience with family-based genetic epidemiology studies. The goal of this study is to identify genes that influence BMD, which may provide new insights into the underlying biology and risk factors of bone disease. PUBLIC HEALTH RELEVANCE: Osteoporosis contributes substantially to disability and morbidity in older populations. The objective of this study is to identify genes that influence bone mineral density in two different populations. Better understanding of the genetics of bone mineral density and osteoporosis may help develop new prevention and treatment strategies that ultimately decrease the public health burden of this disease.